Immunotherapy

Immunotherapy
The combination of immunotherapy with nivolumab (Opdivo) and ipilimumab (Yervoy) may soon represent a new first-line treatment option in patients with early-stage metastatic colorectal cancer (CRC) associated with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Two studies presented at the ESMO 2018 Congress demonstrated the efficacy of this combination in this patient population.
Learning how to activate and harness the immune system—the body’s built-in defense against disease—has brought the field of oncology to the cusp of a cure for at least some, if not many, types of cancer, according to an international authority in immuno-oncology.

The second-generation chimeric antigen receptor (CAR) T-cell therapy, bb2121, engineered to target B-cell maturation antigen, a protein on the surface of certain myeloma cells, displayed continuing efficacy and safety in an update of a phase 1 clinical trial in patients with relapsed or refractory multiple myeloma.

“The wide range of potential immune-related adverse events requires multidisciplinary, collaborative management by providers across the clinical spectrum,” according to Michael A. Postow, MD, and colleagues.
The NCCN’s first guideline for side effects from immunotherapy recognizes a new spectrum of events in patients who are receiving immune checkpoint inhibitor therapy.

Chimeric antigen receptor (CAR) T-cell therapy has had excellent results in late-stage leukemia and varying degrees of success in some other hematologic cancers, but thus far, solid tumors have not responded to this therapy.

Among the 84 patients, 7 had partial responses with the combination of atezolizumab (Tecentriq) and cobimetinib (Cotellic). The median duration of response was 14.3 months.

The combination cohort consisted of 119 patients who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolu­mab 3 mg/kg every 2 weeks. The median follow-up was 13.4 months.

“We find that T-cells with highly activated glycolysis pathways ended up performing worse when we tried to make them into CAR T-Cells. Substituting and supplementing heavily with fatty acids did seem to improve this a little,” said David M. Barrett, MD, PhD, at the 2018 American Association for Cancer Research annual meeting.

The FDA granted accelerated approval to nivolumab based on a notable clinical benefit in a subset of patients who progressed after receiving the standard first-line chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan.

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